Carcinogenesis Advance Access published online on August 6, 2008
Carcinogenesis, doi:10.1093/carcin/bgn181
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Zyflamend® reduces LTB4 formation and prevents oral carcinogenesis in a 7,12-dimethylbenz[
]anthracene (DMBA)-induced hamster cheek pouch model
1 The University of Texas M. D. Anderson Cancer Center, Houston Texas
2 Beijing Hospital for Stomatology, Capital Medical University, Beijing, P. R. China
3 North Carolina Central University, Durham, NC
* Requests for reprints: Robert A. Newman, Ph.D., Department of Experimental Therapeutics, Unit 601, The University of Texas M. D. Anderson Cancer Center, 8000 El Rio Street, Houston, TX 77054. Phone: 713-563-7543; Fax: 713-563-9093; E-mail: rnewman{at}mdanderson.org
Aberrant arachidonic acid (AA) metabolism, especially altered cyclooxygenase and 5-lipoxygenase (5-LOX) activities, have been associated with chronic inflammation as well as carcinogenesis in human oral cavity tissues. Here, we examined the effect of Zyflamend®, a product containing ten concentrated herbal extracts, on development of DMBA-induced inflammation and oral squamous cell carcinoma (SCC). A hamster cheek pouch model was used in which 0.5% 7,12-dimethylbenz[
]anthracene (DMBA) was applied topically onto the left cheek pouch of male Syrian golden hamsters either 3 times/wk for three weeks (short term) or 6 weeks (long term). Zyflamend was then applied topically at one of three different doses (25, 50, 100 µl) onto the left cheek pouch three times for one week (short term study) or chronically for 18 weeks. Zyflamend significantly reduced infiltration of inflammatory cells, incidence of hyperplasia and dysplastic lesions, BrdU-labeling index as well as number of SCC in a concentration-dependent manner. Application of Zyflamend (100 µl) reduced formation of leukotriene B4 (LTB4) by 50% compared to DMBA-treated tissues. The reduction of LTB4 was concentration-dependent. The effect of Zyflamend on inhibition of LTB4 formation was further confirmed with in vitro cell based assay. Adding LTB4 to RBL-1 cells, a rat leukemia cell line expressing high levels of 5-LOX and LTA4 hydrolase, partially blocked anti-proliferative effect of Zyflamend. This study demonstrates that Zyflamend inhibited LTB4 formation and modulated adverse histopathological changes in the DMBA-induced hamster cheek pouch model. The study suggests that Zyflamend might prevent oral carcinogenesis at the post-initiation stage.
Key Words: Zyflamend • DMBA • oral carcinoma • LTB4 • and 5-lipoxygenase
Received March 6, 2008; revised August 1, 2008; accepted August 1, 2008.
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